Histopathological features of organs in a rat model of mamamry carcinogenesis: a reference database

Mammary tumors’ development was induced through the intraperioneal administration of the carcinogen N-methyl-N-nitrosourea (MNU). Animals from group control were injected with the vehicle (saline solution). Animals were sacrificed at 25 weeks-old and the organs were histopathologically evaluated. A higher number of lesions was observed in the organs of animals from group MNU. The animals from group control did not present any lesion in lymph nodes. Independently of the experimental group, the internal organs presented hemodynamic alterations, degenerative and inflammatory changes. Hemodynamic changes may be consequence of euthanasia method. As expected, the higher number and the higher grade of the lesions in group MNU were due to the carcinogen administration.info:eu-repo/semantics/publishedVersio

Realistic aspects behind the application of the rat model of chemically-induced mammary cancer: Practical guidelines to obtain the best results

Cancer is one of the most important public health problems worldwide. Despite the great contribution of in-vitro studies for biomedical research, animals are essential to study diseases’ biopathology and diagnosis, and searching for new preventive and therapeutic strategies. Breast cancer is currently the most common cancer globally, accounting for 12.5% of all new annual cancer cases worldwide. Although the rat model of mammary cancer chemically-induced is widely used to study this disease, there is a lack of standardization in procedures for cancer induction, sample collection, and analysis. Therefore, it is important to provide a practical guide for researchers aiming to work with this model to make the analysis of results more uniform. Thus, in this review, we provide the researchers with a detailed step-by-step guide to implement a rat model of mammary cancer, based on our wide experience in this field, to obtain the best results, maximum throughput of each experiment, and easy comparison among researches

Modelos de cancro da mama: do in vitro para o in vivo

A incidência e mortalidade de cancro da mama têm vindo a aumentar ao longo dos anos. Esta doença foi descrita pela primeira vez no ano 3000 a.C. por Edwin Smith Papyrus como uma doença grave sem tratamento conhecido. Atualmente, continua a ser necessário o delineamento de estratégias de prevenção, deteção e tratamento do cancro da mama. Para tal, é extremamente importante a utilização de modelos alternativos ao Homem. A utilização de animais para fins experimentais iniciou-se há muitos séculos (2000 anos a.C.), com os Babilónios e os Assírios a utilizarem animais para a realização de cirurgias. Os modelos in vitro são relativamente recentes em comparação com os modelos in vivo, uma vez que a primeira linha celular de cancro da mama (BT-20) foi descoberta apenas em 1958 por Lasfargues e Ozzello. Os modelos in vivo são os mais utilizados pois mimetizam quase na sua totalidade o comportamento da neoplasia no organismo. Em 1965, Howell realizou o primeiro estudo de carcinogénese mamária quimicamente induzida em ratos. Posteriormente, surgiu a necessidade da criação de animais geneticamente modificados para reduzir ao máximo as diferenças nos mecanismos tumorais. Mesmo assim, não é possível mimetizar a 100% o processo de carcinogénese humano nestes animais devido à sua elevada complexidade e número limitado de genes. Atualmente existe uma diversidade de modelos in vitro e in vivo para o estudo do cancro da mama. A escolha do modelo animal mais adequado é um dos passos mais importantes no delineamento experimental. Os objetivos do trabalho e o tipo de dados que poderão ser obtidos do modelo animal são aspetos fundamentais a ter em consideração. Todos os modelos apresentam vantagens e desvantagens e a sua seleção merece uma reflexão cuidada à luz dos objetivos do trabalho

Evaluation of renal injury caused by acute volume replacement with hydroxyethyl starch 130/0.4 or Ringer's lactate solution in pigs

This work aimed to evaluate the effects on renal tissue integrity after hydroxyethyl starch (HES) 130/0.4 and Ringer’s lactate (RL) administration in pigs under general anesthesia after acute bleeding. A total of 30 mL/kg of blood were passively removed from the femoral artery in two groups of Large White pigs, under total intravenous anesthesia with propofol and remifentanil. After bleeding, Group 1 (n =11) received RL solution (25 mL/kg) and Group 2 (n = 11) received HES 130/0.4 solution (20 mL/kg). Additionally, Group 3 (n = 6) was not submitted to bleeding or volume replacement. Pigs were euthanized and kidneys were processed for histopathological and immunohistochemical analyses. Minimal to moderate glomerular, tubular, and interstitial changes, as well as papillary necrosis, were observed in all experimental groups. Pre-apoptosis and apoptosis indicators were higher in pigs that received HES 130/0.4, indicating a higher renal insult. Both HES 130/0.4 and RL administration may cause renal injury, although renal injury may be more significant in pigs receiving HES 13/0.4. Results also suggest that total intravenous anesthesia with propofol and remifentanil may cause renal injury, and this effect can be dose related.info:eu-repo/semantics/publishedVersio

Recommendations for Urine and Urinary Bladder Collection in Chemical Carcinogenesis Assays with Rodents

This review describes the technical procedures to collect and process urine and urinary bladder samples, during and at the end of urinary bladder carcinogenesis assays with small rodents. The applications, advantages and disadvantages of each method are also mentioned and discussed

Validation of the rat model of prostate cancer: correlating seminal vesicle lesions with dorsolateral prostate lesions

Background/aim: Lesions in the seminal vesicle are described in the most used protocols for prostate cancer (PCa) induction. This study aimed to characterize the lesions of seminal vesicles associated with a protocol of PCa induction in rats to contribute to better characterization of this model. Materials and methods: Forty-five male Wistar Unilever rats were randomly divided into two control groups: CONT1 (n=10) and CONT2 (n=10); and two PCa-induced groups: IND1 (n=10) and IND2 (n=15), sacrificed at 35 and 61 weeks, respectively. Animals from the induced groups were exposed to a multistep protocol for PCa induction. Animals, seminal vesicles and dorsolateral prostate were weighed. Seminal vesicles and dorsolateral prostate were submitted to histopathological and immunohistochemical analysis. Results: Animals in which PCa was induced had a lower mean body weight when compared with the control animals (p<0.05). The relative mean seminal vesicle weight was higher in groups with PCa when compared with control groups (p<0.05). Although the differences were not statistically significant, animals from the IND2 group developed more lesions than animals from the IND1 and CONT2 groups. It is worth noting that the animals from group IND2 developed papillary adenomas and carcinomas in situ, which were not observed in any other group. Similar to observations in seminal vesicles, animals from group IND2 developed more dorsolateral prostate lesions than animals from the IND1 group (p<0.05). Conclusion: We observed that the longer the exposure to testosterone was, the greater was the incidence of preneoplastic and neoplastic lesions in both the seminal vesicle and the prostate, suggesting that testosterone exposure affects the spectrum of developed lesions

Cytokeratin 7/19 expression inN-diethylnitrosamine-induced mouse hepatocellular lesions: implications for histogenesis International

Hepatocellular carcinoma (HCC) is a common malignancy with poor clinical outcome, whose histogenesis is the subject of intense debate. Specifically, expression ofcytokeratins (CKs) 7 and 19, associated with aggressive biological behaviour, is proposed to reflect a possible progenitor cell origin or tumour dedifferentiation towardsa primitive phenotype. This work addresses that problem by studying CKs 7 and 19expression in N-diethylnitrosamine (DEN)-induced mouse HCCs. ICR mice weredivided into six DEN-exposed and six matched control groups. Samples were takenfrom each group at consecutive time points. Hyperplastic foci (13 lesions) occurredat 29-40 weeks (groups 8, 10 and 12) with diffuse dysplastic areas (19 lesions) andwith one hepatocellular adenoma (HCA) (at 29 weeks). HCCs (4 lesions) wereobserved 40 weeks after the first DEN administration (group 12). CKs 7 and 19showed identical expression patterns and located to large, mature hepatocytes, isolated or in small clusters. Hyperplastic foci and the single HCA were consistentlynegative for both markers, while dysplastic areas and HCCs were positive. Theseresults support the hypothesis that CKs 7 and 19 expression in hepatocellular malignancies results from a dedifferentiation process rather than from a possible progenitor cell origin

Anatomy and imaging of rat prostate: practical monitoring in experimental cancer-induced protocols

The rat has been frequently used as a model to study several human diseases, including cancer. In many research protocols using cancer models, researchers find it difficult to perform several of the most commonly used techniques and to compare their results. Although the protocols for the study of carcinogenesis are based on the macroscopic and microscopic anatomy of organs, few studies focus on the use of imaging. The use of imaging modalities to monitor the development of cancer avoids the need for intermediate sacrifice to assess the status of induced lesions, thus reducing the number of animals used in experiments. Our work intends to provide a complete and systematic overview of rat prostate anatomy and imaging, facilitating the monitoring of prostate cancer development through different imaging modalities, such as ultrasonography, computed tomography (CT) and magnetic resonance imaging (MRI).publishe

Evaluation of renal injury caused by acute volume replacement with hydroxyethyl starch 130/0.4 or Ringer's lactate solution in pigs

This work aimed to evaluate the effects on renal tissue integrity after hydroxyethyl starch (HES) 130/0.4 and Ringer’s lactate (RL) administration in pigs under general anesthesia after acute bleeding. A total of 30 mL/kg of blood were passively removed from the femoral artery in two groups of Large White pigs, under total intravenous anesthesia with propofol and remifentanil. After bleeding, Group 1 (n = 11) received RL solution (25 mL/kg) and Group 2 (n = 11) received HES 130/0.4 solution (20 mL/kg). Additionally, Group 3 (n = 6) was not submitted to bleeding or volume replacement. Pigs were euthanized and kidneys were processed for histopathological and immunohistochemical analyses. Minimal to moderate glomerular, tubular, and interstitial changes, as well as papillary necrosis, were observed in all experimental groups. Pre-apoptosis and apoptosis indicators were higher in pigs that received HES 130/0.4, indicating a higher renal insult. Both HES 130/0.4 and RL administration may cause renal injury, although renal injury may be more significant in pigs receiving HES 13/0.4. Results also suggest that total intravenous anesthesia with propofol and remifentanil may cause renal injury, and this effect can be dose relate

Pulegone and Eugenol Oral Supplementation in Laboratory Animals: Results from Acute and Chronic Studies

Essential oils are natural compounds used by humans for scientific purposes due to their wide range of properties. Eugenol is mostly present in clove oil, while pulegone is the main constituent of pennyroyal oil. To guarantee the safe use of eugenol and pulegone for both humans and animals, this study addressed, for the first time, the effects of these compounds, at low doses (chronic toxicity) and high doses (acute toxicity), in laboratory animals. Thirty-five FVB/n female mice were randomly assigned to seven groups (n = 5): group I (control, non-additive diet); group II (2.6 mg of eugenol + 2.6 mg of pulegone); group III (5.2 mg of eugenol + 5.2 mg of pulegone); group IV (7.8 mg of eugenol + 7.8 mg of pulegone); group V (7.8 mg of eugenol); group VI (7.8 mg of pulegone); and group VII (1000 mg of eugenol + 1000 mg of pulegone). The compounds were administered in the food. Groups I to VI were integrated into the chronic toxicity study, lasting 28 days, and group VII was used in the acute toxicity study, lasting 7 days. Animals were monitored to assess their general welfare. Water and food intake, as well as body weight, were recorded. On the 29th day, all animals were euthanized by an overdose of ketamine and xylazine, and a complete necropsy was performed. Blood samples were collected directly from the heart for microhematocrit and serum analysis, as well as for comet assay. Organs were collected, weighed, and fixed in formaldehyde for further histological analysis and enzymatic assay. Eugenol and pulegone induced behavioral changes in the animals, namely in the posture, hair appearance and grooming, and in mental status. These compounds also caused a decrease in the animals' body weight, as well as in the food and water consumption. A mortality rate of 20% was registered in the acute toxicity group. Both compounds modulated the serum levels of triglycerides and alanine aminotransferase. Eugenol and pulegone induced genetic damage in all animals. Eugenol increased the activity of the CAT enzyme. Both compounds increased the GR enzyme at the highest dose. Moreover, pulegone administered as a single compound increased the activity of the GST enzyme. Histopathological analysis revealed inflammatory infiltrates in the lungs of groups II, III, and IV. The results suggest that eugenol and pulegone may exert beneficial or harmful effects, depending on the dose, and if applied alone or in combination